Objective ·To investigate the mechanism of hemoglobin (Hb)-induced cardiomyocyte injury and the regulatory role of Basigin (BSG) in this process. Methods ·An in vitro model was established by treating H9c2 cardiomyocytes with different concentrations of Hb (0, 7.5, 15.0, and 30.0 μmol/L); cell viability and mortality were detected using the WST-1 assay and flow cytometry. Subsequently, H9c2 cardiomyocytes underwent hypoxia/reoxygenation treatment with low-concentration gradients of Hb (0, 2.5, 5.0, and 7.5 μmol/L) to simulate the pathological microenvironment of ischemia-reperfusion injury, further validating Hb's toxic effects on cardiomyocytes. Multiple cell death inhibitors were used, including a necroptosis inhibitor (necrostatin-1, Nec-1), an autophagy inhibitor (3-methyladenine, 3-MA), a ferroptosis inhibitor (ferrostatin-1, Fer-1), and a pyroptosis inhibitor (VX-765), to investigate the mechanism of Hb-induced cardiomyocyte injury. Bsg mRNA and protein levels were detected by Western blotting and real-time quantitative PCR. Bsg expression was knocked down in H9c2 cardiomyocytes using siRNA; the role of BSG in Hb-induced cardiomyocyte injury and ferroptosis was then verified by the WST-1 assay and flow cytometry. Results ·Under both normoxic and hypoxia/reoxygenation conditions, Hb showed direct toxic effects on H9c2 cardiomyocytes in a concentration-dependent manner. Further investigation showed that, compared with other cell death inhibitors, the ferroptosis inhibitor Fer-1 more significantly alleviated Hb-induced cardiomyocyte injury. Western blotting and real-time quantitative PCR results demonstrated that compared with the control group, Bsg mRNA and protein expression levels were significantly increased in Hb-treated H9c2 cardiomyocytes. Knockdown of Bsg expression decreased the mRNA expression of the ferroptosis marker prostaglandin-endoperoxide synthase 2 (Ptgs2) and alleviated Hb-induced cardiomyocyte injury and death. Conclusion ·Hb may induce myocardial injury by promoting cardiomyocyte ferroptosis; BSG plays a role in this process, and inhibition of its expression can counteract Hb-induced ferroptosis and cardiomyocyte injury.

Objective ·To analyze the correlation between platelet activation indices and xanthine oxidase (XO) activity in patients and the underlying molecular mechanisms. Methods ·Between January 2023 and June 2025, 24 patients with hyperuricemia were recruited from the Department of Rheumatology and the Physical Examination Center of Huashan Hospital, Fudan University. Twenty-four healthy volunteers from the same center during the same period served as the healthy control group. Demographic data (age, gender), comorbidities, and medication history of all subjects were collected, and their fasting venous blood was drawn. Washed platelets were prepared for subsequent assays. The expression levels of P-selectin and platelet activation complex-1 (PAC-1) on the platelet surface were determined by flow cytometry, while platelet XO activity was measured via an absorbance assay. Spearman correlation analysis was performed to evaluate the relationships between uric acid levels, XO activity, and platelet activation markers. The effects of various concentrations of febuxostat on platelet aggregation induced by collagen, adenosine diphosphate (ADP), U46619, and thrombin were assessed. Platelet spreading on fibrinogen was analyzed. Furthermore, thrombin-induced intraplatelet reactive oxygen species (ROS) production was measured. Results ·Compared with the healthy control group, patients in the hyperuricemia group exhibited significantly higher platelet surface expression of P-selectin and PAC-1 (both P<0.05). However, neither marker showed a significant correlation with serum uric acid levels (both P>0.05). Platelet XO activity showed a positive correlation with thrombin-induced P-selectin expression (r=0.453, P=0.001) and PAC-1 expression (r=0.478, P=0.001). Febuxostat at concentrations of 50 μmol/L and 100 μmol/L significantly inhibited collagen, ADP, U46619, and thrombin-induced platelet aggregation and also significantly suppressed the spreading of platelets on fibrinogen. These inhibitory effects were statistically significant (all P<0.05) and intensified with increasing concentrations of febuxostat, demonstrating a concentration-dependent manner. Meanwhile, febuxostat treatment significantly reduced intraplatelet ROS generation in response to thrombin stimulation (P<0.05). Conclusion ·Platelet activation markers are higher in hyperuricemia patients than in the healthy control group. The expression levels of P-selectin and PAC-1 on the platelet surface show a positive correlation with intraplatelet XO activity. XO inhibitors can modulate platelet activation by reducing intracellular ROS production.

Objective ·To evaluate the relevant risk factors and pathophysiological mechanisms of moderate-to-severe secondary tricuspid regurgitation (STR) in acute ST-segment elevation myocardial infarction (STEMI) patients using cardiac magnetic resonance (CMR) imaging. Methods ·A total of 729 STEMI patients who underwent percutaneous coronary intervention (PCI) at Renji Hospital, Shanghai Jiao Tong University School of Medicine, from August 2013 to June 2023 were analyzed. All patients underwent both CMR and transthoracic echocardiography (TTE) examinations within 2‒7 d post-PCI. Patients were stratified into two groups based on TTE findings: significant STR (moderate-to-severe) and non-significant STR (mild or absent). Clinical characteristics, CMR parameters, and the incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) were compared between the groups. Univariate and multivariate Logistic regression analyses were performed to identify independent predictors of significant STR. Results ·Of the 729 enrolled STEMI patients, 53 (7.3%) developed significant STR. Compared to the non-significant STR group (n=676), patients with significant STR were older, had a lower proportion of males, and had a lower prevalence of hyperlipidemia (all P<0.05). Survival analysis revealed a significantly higher cumulative incidence of MACCEs in the significant STR group than in the non-significant STR group (log-rank P<0.001). CMR analysis revealed that the significant STR group exhibited more pronounced left ventricular remodeling and myocardial strain impairment, characterized by an increased left ventricular end-systolic volume index (LVESVi) and reduced left ventricular ejection fraction (LVEF). Additionally, this group showed significantly decreased left ventricular global radial strain (LV-GRS), the absolute value of left ventricular global circumferential strain (LV-GCS), the absolute value of radial peak early diastolic strain rate (rPEDSR), and circumferential peak early diastolic strain rate (cPEDSR) (all P<0.05). Multivariate Logistic regression analysis identified LVESVi (OR=1.030, 95%CI 1.011‒1.049, P=0.002), LVEF (OR=0.963, 95%CI 0.940‒0.986, P=0.002), LV-GRS (OR=0.953, 95%CI 0.913‒0.994, P=0.026), and LV-GCS (OR=1.091, 95%CI 1.011‒1.178, P=0.025) as independent factors associated with significant STR, all of which demonstrated good discriminative performance (all AUC>0.83). Conclusion ·STR occurring acutely in STEMI patients is significantly associated with adverse clinical outcomes. Left ventricular structural remodeling and dysfunction are the key pathophysiological basis for its development. CMR-derived parameters provide crucial evidence for early identification and risk stratification of significant STR.

Objective ·Patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) are at risk of severe complications, such as hypotension and malignant arrhythmias, which directly affect procedural success and patient prognosis. Current clinical practice lacks targeted assessment tools, and traditional assessment tools have limitations in predictive efficacy. This study innovatively applies machine learning methods to construct a precise intraoperative complication prediction model, addressing the insufficient non-linear relationship capture in existing scoring systems and providing an early risk warning tool for surgeons. Methods ·The study included 811 emergency PCI patients who were treated at Shanghai Fengxian Central Hospital from 2019 to 2022, and defined 53 candidate variables. A multi-stage feature engineering framework was employed, including univariate screening, Spearman rank correlation analysis verification, and SHapley Additive exPlanations (SHAP)-based stability optimization. The prediction model was ultimately constructed using the eXtreme Gradient Boosting (XGBoost) algorithm.The primary endpoint was a composite of intraoperative complications, including hypotension, malignant arrhythmias, and severe bradyarrhythmias. Results ·The model identified six core predictive factors: lowest left ventricular ejection fraction (LVEF), culprit vessel in the right coronary artery (CVRCA), culprit vessel presence (CVP), culprit vessel in the left anterior descending artery (CVADA), B-type natriuretic peptide (BNP), and heart rate (HR). The XGBoost model achieved areas under the curve (AUCs) of 0.88 and 0.84 in the training and validation sets, respectively. Conclusion ·This study successfully constructed, for the first time, an intraoperative complication prediction model for AMI patients undergoing PCI based on the XGBoost algorithm. Its predictive performance significantly outperforms that of traditional scoring systems. By automatically selecting key clinical features and effectively capturing complex interactions between variables, the model provides individualized risk assessment for surgeons, thereby supporting clinical decision-making and potentially improving procedural success rates and patient prognosis.

Objective ·To compare the perioperative and short-to-medium-term clinical outcomes of minimally invasive multivessel cardiac surgery-coronary artery bypass grafting (MICS-CABG) and hybrid coronary revascularization (HCR) in patients with multivessel coronary artery disease (CAD), and to evaluate their safety and clinical applicability. Methods ·A retrospective analysis was conducted on 123 patients who underwent minimally invasive coronary artery bypass surgery at the Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, between January 2020 and June 2023. Patients were divided into the MICS-CABG group (n=58) and the HCR group (n=65) based on the surgical approach. Baseline characteristics [smoking history, hypertension, diabetes, chronic obstructive pulmonary disease (COPD), history of cerebral infarction, myocardial infarction, prior percutaneous coronary intervention (PCI), left ventricular ejection fraction (LVEF), number of diseased coronary vessels] and perioperative outcomes [operation time, perioperative transfusion, conversion to median sternotomy, intra-aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO) use, reoperation for any cause, mechanical ventilation duration, intensive care unit (ICU) stay, hospital stay, number of revascularized vessels, 24-hour postoperative drainage volume, mortality, and complications] were compared. Follow-up was conducted at 1, 3, 6, and 12 months postoperatively and every 6 months thereafter, with the primary endpoint being major adverse cardiac and cerebrovascular events (MACCE). Coronary imaging was performed at (12±3) months to assess graft/stent patency. Results ·The MICS-CABG group had a significantly longer operative time (P<0.001), a longer duration of mechanical ventilation (P=0.001), and a higher incidence of early postoperative respiratory failure (32.76% vs 12.31%, P=0.007) compared to the HCR group. However, the MICS-CABG group achieved more complete revascularization (P=0.002). Postoperative 24-hour drainage volume was greater in the MICS-CABG group (P<0.001), but transfusion rates did not differ significantly (6.90% vs 1.54%, P=0.145). Conversion to sternotomy, IABP implantation, and ECMO use were not required in either group. No significant differences were observed in perioperative myocardial infarction, stroke, new-onset atrial fibrillation, mortality, ICU stay, or hospital stay. In the MICS-CABG group, 170 grafts were anastomosed [58 left anterior descending (LAD) grafts and 112 non-LAD grafts], while the HCR group had 65 grafts (all LAD) and 90 PCI-treated vessels. At 1 year, LAD graft patency (93.10% vs 96.92%, P=0.601) and non-LAD target vessel patency (91.96% vs 96.67%, P=0.190) showed no significant differences. The MICS-CABG group patients were followed up for (30±22) months postoperatively, and the HCR group patients were followed up for (31±16) months postoperatively. MACCE rates were low in both groups (MICS-CABG 0 vs HCR 1.54%, P=0.325), with no significant difference in repeat revascularization. Conclusion ·MICS-CABG and HCR demonstrate comparable perioperative safety and short-to-medium-term efficacy in patients with multivessel CAD. While MICS-CABG requires a longer operative time and carries a higher risk of respiratory complications, HCR necessitates stringent PCI eligibility assessment. The choice of procedure should be individualized based on anatomical complexity and cardiopulmonary function.

Objective ·To investigate the causal relationship between gut microbiota and cardiovascular diseases (CVDs) using Mendelian randomization (MR). Methods ·Instrumental variables included genetic loci from gut microbiota data provided by the MiBioGen consortium (n=18 340) and CVD data from the IEU Open GWAS database, covering four CVD types: atrial fibrillation (n=1 030 836), coronary artery disease (n=547 261), hypertension (n=20 526), and heart failure (n=977 323). The inverse variance weighted (IVW) method was employed as the primary analytical approach. Additionally, Cochran's Q test was used to assess heterogeneity of genetic instruments, the MR-Egger intercept test to evaluate horizontal pleiotropy, and leave-one-out analysis to examine the sensitivity of single-nucleotide polymorphisms (SNPs) on the exposure-outcome causal relationship. The MR Steiger test was applied to validate the causal direction between gut microbiota and CVDs. Results ·The IVW analysis indicated that Victivallales (OR=0.939), Howardella (OR=0.939), Anaerostipes (OR=0.922), Bifidobacteriaceae (OR=0.916), Lentisphaeria (OR=0.936), Odoribacter (OR=0.909), Intestinibacter (OR=0.933), Lentisphaerae (OR=0.926), and Bifidobacteriales (OR=0.916) were protective factors against atrial fibrillation, while Catenibacterium (OR=1.057), Lachnospiraceae UCG008 (OR=1.051), Streptococcus (OR=1.089), and Victivallis (OR=1.038) were risk factors. For coronary artery disease, Lactobacillales (OR=0.919) and Parabacteroides (OR=0.866) were protective factors, while Veillonellaceae (OR=1.065), Lachnoclostridium (OR=1.093), Lachnospiraceae (OR=1.094), Oxalobacter (OR=1.062), and Odoribacter (OR=1.160) were risk factors. For hypertension, Mollicutes RF9 (OR=0.851), Coriobacteriia (OR=0.803), Coriobacteriales (OR=0.803), Coriobacteriaceae (OR=0.803), and Intestinibacter (OR=0.819) were protective factors, while Christensenellaceae R7 group (OR=1.218), Desulfovibrio (OR=1.167) ,and Peptococcaceae (OR=1.230) were risk factors. For heart failure, Bacillales (OR=0.955) and Anaerostipes (OR=0.899) were protective factors, while Ruminococcus UCG009 (OR=1.107), Eubacterium oxidoreducens group (OR=1.117), Selenomonadales (OR=1.106), Negativicutes (OR=1.107), Eubacterium eligens group (OR=1.139), and Flavonifractor (OR=1.144) were risk factors. Cochran's Q test showed no heterogeneity among SNPs of gut microbiota causally associated with CVDs (all P>0.05). The pleiotropy test found no evidence of horizontal pleiotropy (all P>0.05). Leave-one-out sensitivity analysis confirmed the robustness of the results. The MR Steiger directionality test supported the causal direction from gut microbiota (exposure) to CVDs (outcome). Conclusion ·Some gut microbiota have significant causal effects on CVDs; altering their abundance may influence CVD risk, providing potential targets for microbiota-based intervention strategies.

Objective ·To investigate the effects of nitrogen dioxide (NO₂) exposure timing and concentration on vascular endothelial dysfunction (VED) in elderly individuals using flow-mediated dilation (FMD) technology. Methods ·A cross-sectional study was conducted among elderly participants who underwent FMD testing at Tongren Hospital, Shanghai Jiao Tong University School of Medicine, between 2020 and 2022. All participants completed detailed questionnaires and clinical examinations, including demographic characteristics, lifestyle factors, and medical history. Individual NO₂ exposure levels were obtained by matching residential addresses with pollution data grids from the Tracking Air Pollution in China (TAP) platform. Generalized additive models combined with distributed lag non-linear models (DLNM) were employed to analyze the impact of NO₂ on FMD and VED, with adjustments for meteorological factors, individual characteristics, and health status as potential confounders. Results ·A total of 812 eligible participants were included after rigorous screening. The results demonstrated that NO₂ exposure was significantly associated with decreased FMD at lag days 1, 2, and 5 (P=0.003, P=0.034, P=0.022), while the risk of VED increased significantly at lag days 5 and 6. Cumulative effect analysis revealed a significant dose-response relationship between NO₂ concentrations (35‒85 μg/m³) and FMD reduction (P<0.05). Subgroup analysis indicated that participants without dyslipidemia or a history of coronary artery disease (CAD) were more susceptible to short-term NO₂ exposure. Conclusion ·This study systematically revealed, for the first time, that short-term NO₂ exposure has a negative impact on vascular endothelial function in elderly individuals, exhibiting distinct temporal patterns and concentration thresholds. NO₂ exposure within 1‒6 d significantly impaired endothelial function, with the most pronounced effects observed on day 5. Notably, clinically "healthy" elderly individuals (without hyperlipidemia or CAD) demonstrated higher susceptibility. These findings not only support the critical role of NO₂ in vascular endothelial injury but also provide important evidence for elucidating the mechanisms by which air pollutants contribute to cardiovascular diseases through vascular dysfunction. The study holds significant implications for developing targeted air pollution prevention strategies for the elderly population.

Objective ·To construct a cardiovascular-kidney-metabolic (CKM) index based on the Global Burden of Disease (GBD) 2021 study, systematically evaluate the synergistic burden of cardiovascular diseases, chronic kidney diseases, and metabolic disorders, and reveal their spatiotemporal distribution patterns and interrelationships worldwide. Methods ·The data were derived from the GBD 2021 project, encompassing 204 countries and regions over the period from 1990 to 2021. The disability-adjusted life year (DALY) rates for ischemic heart disease, chronic kidney disease, and type 2 diabetes mellitus were extracted, age-standardized DALY rates were calculated, and then the CKM index was computed through equal-weighted averaging of these rates after Z-score standardization. The Joinpoint regression models were applied to the CKM index time series for segmented trend fitting, to identify turning points and annual percentage changes at different developmental stages. Countries and regions were categorized and compared according to their socio-demographic index (SDI) levels. Spearman's rank correlation was used to assess the correlations among DALY rates for the three disease categories. Results ·In 2021, the global CKM index value was 0.201. Temporal trend analysis showed that global CKM syndrome burden generally increased from 1990 to 2021, with an average annual increase of 0.002 9. Among these, middle-SDI countries showed the most significant growth, with CKM index rising from -0.130 to 0.783, representing an average annual increase of 0.029 4. High-middle SDI and low-middle SDI countries also demonstrated steady upward trends, with average annual increases of 0.009 7 and 0.009 2, respectively. In high-SDI countries, the CKM index declined from 0.847 in 1990 to its lowest point of 0.783 in 2010, and then rose slightly to 0.792 in 2021. Correlation analysis across 204 countries and regions globally revealed varying degrees of positive correlation among the three types of diseases in terms of DALY rates, with the strongest correlation observed between chronic kidney disease and type 2 diabetes mellitus (r=0.66, P<0.001), while the correlation between ischemic heart disease and chronic kidney disease was weaker (r=0.20, P=0.004). Conclusion ·The CKM index developed in this study provides a categorized and quantitative tool for assessing the burden of multimorbidity. The application of CKM index analysis revealed that cardiovascular diseases, chronic kidney diseases, and metabolic diseases not only share common risk factors but also have synergistic pathological pathways, which should be key clues for global chronic disease prevention and control. Public health policies should break down system silos, strengthen rapid identification and comprehensive management of CKM, and improve the efficiency of chronic disease prevention and treatment.

Heart failure is a complex clinical syndrome resulting from structural and functional impairments of the heart, leading to diminished cardiac output and an inability to fulfill the body's metabolic requirements. Perturbations in myocardial energy metabolism represent a central hallmark of heart failure, characterized by altered substrate utilization, mitochondrial dysfunction, and elevated oxidative stress, all of which contribute critically to disease progression. Given the fundamental role of metabolic homeostasis in sustaining cardiac performance, pharmacological agents that target metabolic pathways, collectively termed metabolic modulators, have gained prominence as promising therapeutic strategies for heart failure. For instance, fatty acid oxidation inhibitors such as perhexiline act by suppressing carnitine palmitoyltransferase Ⅰ/Ⅱ (CPT1/2), thereby reducing fatty acid β-oxidation and improving the efficiency of cardiac energy metabolism. Similarly, 3-ketoacyl-coenzyme A thiolase (3-KAT) inhibitors, such as trimetazidine, enhance glucose oxidation, thereby improving myocardial energy supply. Sodium-glucose cotransporter 2 (SGLT2) inhibitors (e.g., empagliflozin) not only exert hypoglycemic effects but also confer cardioprotective benefits through pleiotropic mechanisms, although their detailed metabolic actions remain under investigation. Furthermore, mitochondrial-targeting peptides, such as elamipretide, preserve mitochondrial integrity and function by stabilizating cardiolipin, thereby providing additional cardioprotection. Although several metabolic modulators have demonstrated encouraging results in preclinical and early clinical studies, their long-term efficacy and safety profiles await validation in large-scale randomized trials. This review synthesizes recent advances in the development of metabolic modulators for heart failure, providing insights into basic research and the translation of clinical treatments.

Ventricular remodeling following myocardial infarction (MI) and its associated myocardial fibrosis represent a core pathological mechanism in the progression of heart failure. Accumulating evidence confirms that the spatiotemporal dynamics of immune cells play a crucial role in post-MI ventricular remodeling, spanning the entire process of cardiac inflammation, tissue repair, and fibrosis. MI not only triggers a local inflammatory response but also remotely regulates hematopoietic organs such as the bone marrow and spleen via pathways including inflammatory factor release and sympathetic nervous system activation. This drives hematopoietic stem/progenitor cells (HSPCs) to differentiate with a bias toward the myeloid lineage, resulting in a hematopoietic imbalance phenomenon described as "myeloid upsurge-lymphoid decline". This imbalance is characterized by excessive proliferation and release of proinflammatory myeloid cells, such as neutrophils and monocytes/macrophages, alongside a relative reduction in lymphoid cells like T cells and B cells. This systemic immune imbalance reshapes the immune cell composition in the heart and peripheral organs. It exacerbates sustained cardiac inflammation, oxidative stress, cell apoptosis, and excessive extracellular matrix deposition, ultimately leading to aggravated cardiac fibrosis, ventricular dilation, and systolic function deterioration. It is a key driver of adverse post-MI remodeling and the onset of heart failure. This article aims to systematically explore the spatiotemporal dynamics and functional characteristics of immune cell subsets driven by this post-MI hematopoietic imbalance. Furthermore, it proposes novel intervention strategies focused on precisely modulating hematopoietic stem cell differentiation pathway and key immune cell subsets. These strategies aim to improve the cardiac inflammatory microenvironment, delay the fibrotic process, and inhibit adverse ventricular remodeling, thereby offering potential therapeutic targets for preventing and treating post-MI heart failure.

Pulmonary arterial hypertension (PAH) is a complex cardiopulmonary disease characterized by persistent constriction and remodeling of the pulmonary arterioles, leading to sustained elevation of pulmonary arterial pressure, right ventricular remodeling, and ultimately right heart failure. Although current clinical therapies mainly alleviate symptoms by targeting the imbalance between vasoconstriction and vasodilation, the overall prognosis remains poor and the mortality rate continues to rise, highlighting the urgent need for novel therapeutic strategies. Mitochondria serve as the primary energy source for cells, generating ATP through oxidative phosphorylation (OXPHOS). However, this process generates reactive oxygen species (ROS), which can damage proteins, lipids, and DNA, thereby exacerbating cellular dysfunction. As a crucial mechanism for maintaining cellular homeostasis, mitophagy facilitates the recognition and clearance of damaged mitochondria, thereby ensuring balanced cellular energy metabolism. Recent studies have revealed a dual-faceted role of mitophagy in the pathogenesis and progression of PAH. On the one hand, mitophagy may be moderately activated during the early stages of PAH to clear damaged mitochondria and suppress abnormal cell proliferation; on the other hand, with PAH progression, excessive mitophagy activation occurs alongside abnormal proliferation of various cell types, leading to pulmonary vascular and right ventricular remodeling. This paper reviews recent literature to elucidate the role of mitophagy in pulmonary vascular and right ventricular remodeling at different stages of PAH, aiming to provide a theoretical basis for developing more effective therapeutic interventions for PAH.

Cardiovascular injury and repair rely on the coordinated recruitment, proliferation, and differentiation of multiple cell types. As a heterogeneous cell population defined by the cluster of differentiation 34 (CD34) protein, CD34⁺ cells have long been regarded as key targets for cardiovascular regeneration and repair. These cells exhibit pronounced heterogeneity and pluripotent differentiation potential. Under the regulation of specific microenvironmental signals, they can differentiate into multiple lineages, such as endothelial cells, smooth muscle cells, fibroblasts, and inflammatory cells, thereby contributing to endothelial repair, tissue fibrosis, and immune modulation. In cardiovascular disease, CD34⁺ cells exert dual effects: they may facilitate tissue repair and regeneration while also potentially exacerbating pathological injury. Although CD34⁺ cell therapies have shown therapeutic promise in cardiovascular diseases, their clinical translation still faces numerous challenges and bottlenecks. Here, current evidence on the sources, differentiation trajectories, and functional heterogeneity of CD34⁺ cells is synthesized, and recent advances spanning basic research and clinical translation are summarized, with the aim of refining mechanistic understanding and informing the development of precise therapeutic strategies.

The circadian rhythm of mammals spans approximately 24 h and is of great significance in maintaining life activities and contributing to the occurrence and progression of various diseases. This intrinsic rhythm is primarily regulated by transcription-translation feedback loops (TTFLs) mediated by core circadian molecules. Circadian genes participate in cardiovascular disease by regulating metabolism, oxidative stress, and inflammatory responses, and play a key role in myocardial infarction. In recent years, with advances in circadian gene research, the underlying molecular mechanisms in myocardial infarction have become increasingly elucidated. This review summarizes the specific molecular mechanisms and clinical research evidence related to core circadian molecules (such as BMAL1, CLOCK, PER, and CRY) in the context of myocardial infarction, explores the therapeutic potential of circadian genes, and discusses current research challenges and future directions in this field. These findings indicate that targeting circadian genes may have promising clinical applications, and could provide new strategies for the treatment of myocardial infarction.

Left ventricular hypertrophy (LVH) is a form of myocardial remodeling characterized by thickening of left ventricular wall and increased myocardial mass. It is not only associated with the incidence and mortality of various cardiovascular diseases such as heart failure, coronary artery disease, and arrhythmias, but is also considered an independent risk factor for cognitive dysfunction. Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disorder of the central nervous system characterized by progressive cognitive impairment and behavioral deficits. Although the relationship between cardiovascular diseases and cognitive dysfunction has been widely investigated, the mechanisms through which LVH affects the core pathology of AD are not yet fully elucidated. This article provides a comprehensive systematic overview regarding the relationship between AD and cardiovascular diseases, the comorbidity of LVH and AD, and their direct pathological mechanisms, offering novel perspectives for advancing the exploration of heart-brain axis interactions.

Atherosclerosis (AS), a chronic vascular inflammatory disease characterized by scattered and deep-seated lesions, is a major cause of cardiovascular disease. Efficient drug delivery is crucial for enhancing therapeutic efficacy in this condition. Nanomaterials exhibit significant advantages in drug delivery systems owing to their unique physicochemical properties. Through targeted surface functionalization, they enable precise drug targeting, promote enhanced accumulation at pathological sites, reduce off-target biodistribution, and ultimately improve both therapeutic efficacy and safety profiles. Nano-delivery systems, categorized based on material characteristics into four major classes—lipid-based, polymeric, inorganic, and biomimetic nanocarriers—have multifunctional composite designs that support multimodal synergistic therapies (e.g., photothermal conversion and magnetic-responsive imaging-guided therapy). These approaches hold significant potential for enhancing therapeutic efficiency in AS management. This review synthesizes recent advances in nanocarrier-based strategies for AS management, focusing on the synthesis of diverse nanocarrier types, targeting mechanisms, and multimodal applications. It covers representative achievements ranging from basic research to preclinical studies and partial clinical trials, while outlining future development directions for nanotechnology-based therapeutic strategies and providing critical perspectives on technical innovations and persistent translational hurdles in this field.

Drug-induced cardiotoxicity, as a major global public health challenge, has led to substantial consumption of medical resources and significant economic losses. Recent studies have revealed that the cannabinoid type 1 receptor (CB1R) plays an important role in various types of drug-induced cardiac injury. This article systematically reviews the molecular characteristics of CB1R and its dual roles in cardiovascular physiology and pathophysiology, with a focus on its molecular mechanisms in cardiotoxicity induced by antipsychotics, anticancer drugs, cannabis, and synthetic cannabinoids. As a key component of the endocannabinoid system, CB1R is widely distributed in cardiomyocytes, endothelial cells, and immune cells. Under normal physiological conditions, it contributes to the homeostatic regulation of heart rate, blood pressure, and cardiovascular contractile activity. It participates in pathological processes, including cardiac electrophysiological disturbances, inflammatory responses, and myocardial fibrosis, through modulation of ion channel activity, release of inflammatory factors, and oxidative/nitrative stress. It is also involved in the mechanisms underlying drug-induced cardiotoxicity. CB1R represents a common pathway in the cardiotoxicity of multiple drugs and may become an important target for the prevention and treatment of drug-induced cardiotoxicity. Future research needs to further elucidate the regulatory mechanisms of CB1R under different pathological conditions and explore precise interventions targeting CB1R to balance therapeutic benefits of drugs against cardiovascular risks.